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1.
JCEM Case Rep ; 2(9): luae158, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39238944

ABSTRACT

We present a patient who had surgically confirmed CD but without the full cushingoid phenotype despite markedly elevated cortisol. Nonpathologic causes of elevated ACTH and cortisol were eliminated as were pathogenic variants in the glucocorticoid receptor gene. Further studies of urine metabolites, cortisol half-life, and the ratios of cortisone to cortisol conversion revealed impaired 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity. There have only been 2 prior reports of impaired 11ß-HSD1 resulting in lack of classic cushingoid features in the past 2 decades. Our patient's presentation and previous reports demonstrate the key role of 11ß-HSD1 in modulating intracellular cortisol concentration, therefore shielding the peripheral tissues from the effects of excess cortisol. When patients present with markedly elevated cortisol but without classic cushingoid features, impaired 11ß-HSD1 should be considered in the differential diagnosis.

2.
J Endocrinol Invest ; 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39305441

ABSTRACT

PURPOSE: Glucocorticoid-mediated hypercoagulability can persist in patients with endogenous Cushing syndrome (CS) after curative surgery and may transiently worsen early postoperatively. These studies aimed to characterize coagulation markers at baseline in patients with CS and the impact of relacorilant or remission post-surgery in an open-label, phase 2 study (NCT02804750) and a retrospective, longitudinal, surgical cohort study. METHODS: In the relacorilant study, 34 patients received relacorilant (100-200 mg/day for up to 12 weeks or 250-400 mg/day for up to 16 weeks) and had postbaseline data. Coagulation markers were assessed before and during treatment. In the surgical study, conducted at "Federico II" University of Naples, Italy, coagulation markers were assessed in 30 patients before surgery and after biochemical remission. RESULTS: In the relacorilant study, significant mean changes from baseline to last observed visit were reported in factor VIII (- 18.9%, P = 0.022), activated partial thromboplastin time (aPTT) (+ 1.5 s, P = 0.046), and platelet count (- 68.8*109/L, P < 0.0001), whereas von Willebrand factor was unchanged. In the surgical study, the mean time to hemostasis assessment was 6.2 months. Significant mean changes from baseline to hemostasis assessment were reported in factor VIII (- 24.2%, P = 0.044), von Willebrand factor (- 20.6%, P = 0.018), and aPTT (+ 2.0 s, P = 0.031), whereas platelet count was unchanged. CONCLUSIONS: Several coagulation markers improved in patients with CS after 3-4 months of relacorilant treatment and within an average of 6 months after surgery. Relacorilant's positive effects on coagulation markers support further investigation of its use preoperatively in patients with CS or in patients who are not eligible for surgery. CLINICAL TRIAL REGISTRATION NUMBER: NCT0280475 (registration date: 15 June 2016).

3.
Cureus ; 16(8): e66615, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39258048

ABSTRACT

In adults, Cushing's syndrome (CS) caused by tumours that produce adrenocorticotropic hormone (ACTH) outside of the pituitary gland is quite prevalent. However, it is uncommon in children and teenagers. Ectopic ACTH syndrome (EAS) is a rare occurrence in young children, accounting for less than 1% of cases. Nevertheless, when it does occur, it tends to be a severe condition due to the profound hypercortisolism that can occur independently of the tumour. Consequently, EAS should be regarded as a critical endocrine emergency, necessitating prompt action in terms of diagnostic procedures and therapeutic interventions. A 14-year-old White female from the United Kingdom (UK) presented with a two-week history of hands and feet swelling, accompanied by a non-itchy rash on the face, back, and chest for one week. Initial investigations revealed hypokalemic alkalosis, hyperglycaemia, elevated serum and 24-hour urinary cortisol, and high ACTH level. Further investigations confirmed EAS, and to find out the primary tumour location, a contrast-enhanced thoracic CT scan was done and identified a 5x3 cm mass with enhanced thymic shadow. Increased radioactivity uptake in the left upper chest along with widespread GAD-avid metastatic disease unveiled by Gallium-DOTA-TATE PET scan. An abdominal MRI, detecting multiple liver deposits, prompted a liver biopsy, revealing a malignant tumour with neuroendocrine differentiation. The patient was diagnosed with EAS with a primary neuroendocrine tumour of the thymus and metastasis. This case underscores the significance of considering EAS in patients with a diagnosis of CS, especially in young individuals with no known risk factors.

5.
BMC Neurol ; 24(1): 355, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39304804

ABSTRACT

BACKGROUND: Several cases of autoimmune disease onset after treatment for Cushing's syndrome have been reported. CASE PRESENTATION: Herein, we report a case of myasthenia gravis crisis in a 51-year-old woman 2 months after adrenalectomy for adrenal Cushing's syndrome accompanied by takotsubo cardiomyopathy. The resolution of excessive endogenous cortisol after adrenalectomy may have triggered the onset of previously latent myasthenia gravis. CONCLUSIONS: Observing the similarities in symptoms between myasthenia gravis and adrenal crisis, which can sometimes be challenging to differentiate, is essential. Moreover, the presence of takotsubo cardiomyopathy as a non-motor manifestation of myasthenic crisis must be noted.


Subject(s)
Adrenalectomy , Cushing Syndrome , Myasthenia Gravis , Takotsubo Cardiomyopathy , Humans , Myasthenia Gravis/complications , Myasthenia Gravis/diagnosis , Myasthenia Gravis/surgery , Takotsubo Cardiomyopathy/etiology , Female , Middle Aged , Adrenalectomy/adverse effects , Cushing Syndrome/surgery , Cushing Syndrome/etiology , Cushing Syndrome/complications
6.
Endocrine ; 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39287756

ABSTRACT

OBJECTIVE: To compare clinical and hormonal data, neuroendocrine neoplasia (NEN) localization, treatment, and survival outcomes in ectopic Cushing's syndrome (ECS) by sex. METHODS: Eleven experienced centers from our country participated in this retrospective study. The clinical and hormonal features, tumor imaging, pathological results, treatment modalities, and disease courses of the patients were evaluated. RESULTS: 28 female and 26 male patients with ECS were compared. The mean age at diagnosis, clinical characteristics, and hormonal evaluation results were similar. However, insulin-requiring diabetes mellitus (p = 0.04) and osteoporosis with fractures were more common in males (p = 0.03). While more patients with increased DHEA-S levels than the upper limit of normal were found to be higher in females, central hypothyroidism were higher in males (p = 0.02). At the diagnosis, 36 NENs (68% of females and 69% of males) were localized. Small cell lung carcinoma was higher in males (p = 0.02), and the frequency of other NENs was not different. Curative surgery was performed on 61% of females and 46% of males. Tumor size, Ki-67 labeling index, positive ACTH immunostaining, local lymph node and distant metastasis rates were similar in both sexes. In the follow-up, the tumor became visible in 7 of 10 females and 4 of 8 males after medical treatment and/or bilateral adrenalectomy. The remission rates (65% of females, 62% of males) and NEN-related death rates (14% of females, 30% of males) were similar. CONCLUSION: While ECS has a similar disease course in many aspects in males and females, hyperglycemia and osteoporosis are more severe in males.

7.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(6): 825-831, 2024 Jun 28.
Article in English, Chinese | MEDLINE | ID: mdl-39311777

ABSTRACT

Cushing syndrome (CS) is an endocrine-metabolic disorder characterized by hypercortisolism. Elevated cortisol levels can induce a hypercoagulable state, increasing the risk of venous thromboembolism (VTE). Both pituitary-origin Cushing disease (CD) and adrenal-origin non-adrenocorticotropic hormone (ACTH)-dependent CS are primarily treated with surgery. The dual impact of surgery and the underlying disease further elevates the risk of VTE, potentially leading to pulmonary embolism, which poses a severe threat to patient survival. Additionally, CS patients in a hypercoagulable state have a higher incidence of cardiovascular diseases and VTE, and even mortality compared with the general population. Untreated active CS patients have a 17.8-fold increased risk of VTE compared to the general population. In recent years, the relationship between the hypercoagulable state in CS and VTE has garnered increasing attention from clinicians. A better understanding of the clinical epidemiological characteristics, pathophysiological mechanisms, and clinical prevention and treatment of VTE and pulmonary embolism in CS can provide valuable references for the standardized use of prophylactic anticoagulant therapy in CS patients.


Subject(s)
Cushing Syndrome , Pulmonary Embolism , Venous Thromboembolism , Humans , Cushing Syndrome/complications , Venous Thromboembolism/etiology , Pulmonary Embolism/etiology , Risk Factors , Thrombophilia/complications , Thrombophilia/etiology , Anticoagulants/therapeutic use
8.
J Pak Med Assoc ; 74(9): 1716-1717, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39279087

ABSTRACT

The adrenal gland is a player in the Ominous Octet of obesity, which lists eight endocrine contributors to the development of obesity. Baro-adrenal axis describes the bidirectional, multifaceted link between weight homoeostasis and adrenal function, in health and disease. This communication lists the various ways in which adrenal function influences, and is impacted by, obesity.


Subject(s)
Adrenal Glands , Obesity , Humans , Obesity/physiopathology , Adrenal Glands/physiology , Adrenal Glands/physiopathology , Sympathetic Nervous System/physiopathology , Sympathetic Nervous System/physiology
9.
Pituitary ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39251540

ABSTRACT

CONTEXT: The hypothalamic-pituitary-adrenal axis is a critical regulator of circadian rhythm in humans. Impaired sleep adversely affects metabolic, emotional, and cognitive health. OBJECTIVE: To characterize sleep disturbances in patients with active and treated Cushing's syndrome (CS), and identify factors associated with impaired sleep in treated patients. DESIGN: Single-center cross-sectional study. METHODS: Patients with pituitary or adrenal CS enrolled in an observational study completed Nottingham Health Profile (NHP), CushingQoL, and Hospital Anxiety and Depression assessments. Cross-sectional analysis was conducted including patients with active and treated disease. RESULTS: 113 (94 female) patients with CS were included, 104 pituitary and 9 adrenal, with mean age at diagnosis of 43.9 ± 13.4 years. Mean and maximum duration of follow up was 5.1 and 23 years. Mean NHP sleep score was lower (i.e., improved) in patients with treated vs. active disease (29.6 ± 30.2 vs. 51.9 ± 30.9, p = 0.0005), as was CushingQoL sleep score (p = 0.015), but 41.5% of patients with treated disease stated they often or always had trouble sleeping. The proportion of treated vs. active patients taking medication for sleep, mood, or pain was not different. Neither NHP nor CushingQoL pain scores were lower in treated vs. active patients (p = 0.39 and 0.53). In patients with treated CS, anxiety and depression correlated with worse sleep scores. CONCLUSIONS: Patients with treated CS report improved sleep quality compared to those with active disease, but almost half of treated patients still report sleep challenges. The need for sleep medications, reported by one third of patients, was not different after CS treatment. Ongoing mood disturbances may play a role in persistent sleep disruption. Further work should focus on determinants of sleep impairments in treated CS patients.

10.
Cureus ; 16(8): e66045, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39224726

ABSTRACT

Cushing's disease (CD) is characterized by a high rate of hypogonadism and infertility. It is difficult to detect CD in pregnant women who present with symptoms such as weight gain, striae, headache, backache, and pedal edema that overlap with the physiological changes of pregnancy. In this paper, we present three cases of CD likely missed during pregnancy and later also discuss the approach to diagnosis and management of CD in pregnancy.

11.
Horm Res Paediatr ; : 1-10, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39102796

ABSTRACT

INTRODUCTION: Adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS) is very rare condition in children. Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of CS, which in most cases occurs in the context of Carney complex (CNC). CNC is a rare autosomal-dominantly inherited genetic syndrome, usually due to pathogenic variants of the PRKAR1A (regulatory subunit R1A of the protein kinase A) gene located at 17q22-24. The clinical picture is characterized by spotty skin pigmentation, cardiac, cutaneous, and mammary myxomas, melanocytic schwannomas, endocrinopathies, and tumours of the endocrine glands (mostly adrenal, pituitary, and thyroid). CASE PRESENTATION: A 10-year-old boy first came to our outpatient clinic due to severe obesity. During the first 3 months of follow-up, the height growth rate was normal, but the response to dietary-behavioural indications was poor in terms of weight loss. Later, 10 months after the last evaluation, there was evidence of significant worsening of obesity, growth failure (growth velocity 0.7 cm/year), arterial hypertension, and the occurrence of violaceous striae at the trunk and root of the limbs. Endocrinological causes of obesity associated with growth failure were investigated. The circadian rhythm of cortisol, ACTH, and cortisoluria were suggestive of ACTH-independent hypercortisolaemia. Iatrogenic causes were ruled out. Adrenal ultrasound and computer tomography scan were performed, which initially indicated the presence of a nodule or hyperplasia of the medial arm of the left adrenal gland. Conversely, magnetic resonance imaging showed a significant increase in the global dimensions of the adrenals with a bilateral micronodular appearance. In light of the association between ACTH-independent hypercortisolism and bilateral micronodular adrenal hyperplasia, a genetic investigation was performed, which found a pathogenic variant of the PRKAR1A gene. The patient was begun on treatment with metyrapone which was well tolerated over a 2-year period. The clinical picture has slightly improved, cortisoluria returned and remains within normal limits, but ACTH suppression persists. CONCLUSION: This is the first report on the clinical and biochemical effects of 2-year medical treatment with metyrapone of PPNAD-related hypercortisolaemia in a paediatric patient with CNC. Currently, there are no established protocols for the management of hypercortisolism in PPNAD and data are scarce, especially in the paediatric field. Medical therapies may play a role in reducing the need, at least initially, for patients to undergo bilateral adrenalectomy. However, further studies on larger case series are needed to clarify this aspect. In cases of CS due to PPNAD in which medical therapy was the initial approach, in the absence of clear clinical, auxological, and biochemical improvements, metyrapone may have to be discontinued in favour of another approach, including surgery.

12.
Ann Surg Treat Res ; 107(2): 100-107, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39139828

ABSTRACT

Purpose: The aim of this study is to investigate the effect of obesity on the results of laparoscopic adrenal surgery in patients with Cushing syndrome. Methods: This retrospective study was performed in Department of General Surgery at Erciyes University School of Medicine between January 2010 and January 2023. Our analysis included Cushing syndrome patients who underwent unilateral laparoscopic adrenalectomy (LA) with the transabdominal lateral approach. All patients were evaluated in terms of age, sex, tumor diameter, body mass index (BMI), American Society of Anesthesiologists physical status classification, morbidities, surgery history, tumor side, operative time, conversion to open surgery, complications, and length of hospital stay. Results: A total of 90 patients (75 females and 15 males) underwent a transperitoneal LA. Patients were divided into 2 groups according to their BMI: obese group (≥30 kg/m2; n = 53, 58.8%) and nonobese group (<30 kg/m2; n = 37, 41.2%). All patients were classified into 3 subgroups: obese patient group, BMI ≥30-39 kg/m2 (n = 23); morbidly obese patient group, BMI ≥40 kg/m2 (n = 14); and nonobese patient group, BMI <30 kg/m2 (n = 53). There was no significant difference in intraoperative complications, conversion to open surgery, operative time, or length of hospital stay between the groups. Only conversion to open surgery was a risk factor for postoperative complications in univariate and multivariate analyses (odds ratio, 15.4; 95% confidence interval, 1.277-185.599; P = 0.031). Conclusion: Our results showed that LA is safe and effective in patients with Cushing syndrome with morbid obesity, allowing acceptable morbidity and length of hospital stay.

13.
Biochem Pharmacol ; 229: 116475, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39128585

ABSTRACT

This Virtual Special Issue on Adipose tissue in health and disease features 26 original articles from different international contexts. It expands our understanding of the adipose tissue as an essential organ involved in relevant physiological functions such as reproduction, metabolism, energy balance, endocrinology, circadian rhythm, and inflammation. The focus is on the adipose tissue as a common key mediator of different severe metabolic pathologies including insulin resistance, liver diseases, cardiometabolic diseases, diabetes, lipodystrophy, Cushing's syndrome, obesity, and polycystic ovary syndrome. This adipose tissue-associated diseases are linked with a high mortality and increased health care costs worldwide. Thus, the 26 contributions of this Special Issue aim at identifying molecular mechanisms by which the adipose tissue is involved in the progression of its associated pathologies. Deeper understanding of these mechanisms in health and disease and the context-dependent parameters shaping them, is likely key to decipher the full potential of the adipose tissue for novel therapeutic approaches and strategies for managing complications associated with obesity and the metabolic syndrome.

14.
Front Endocrinol (Lausanne) ; 15: 1373101, 2024.
Article in English | MEDLINE | ID: mdl-39145316

ABSTRACT

Context: Few studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing's syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear. Objective: To compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function. Methods: We prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment. Results: Patients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P<0.05). No statistical difference was found in cognitive functions between patients with MACS and CS. Logistic regression analysis showed that patients with MACS (odds ratio [OR]=3.738, 95% confidence intervals [CI]: 1.329-10.515, P=0.012) and CS (OR=6.026, 95% CI: 1.411-25.730, P=0.015) were associated with an increased risk of immediate memory impairment. Visuospatial/constructional, immediate and delayed memory scores of MACS patients were significantly improved at 12 months compared with pre-operation in the surgical treatment group (all P<0.05), whereas there was no improvement in the conservative treatment group. Conclusion: Patients with MACS have comparable cognitive impairment as patients with CS. Cognitive function was partially improved in patients with MACS after adrenalectomy. The current data support the inclusion of cognitive function assessment in the clinical management of patients with MACS.


Subject(s)
Adrenalectomy , Cognitive Dysfunction , Cushing Syndrome , Humans , Female , Male , Cushing Syndrome/surgery , Cushing Syndrome/complications , Cushing Syndrome/therapy , Cushing Syndrome/psychology , Cognitive Dysfunction/etiology , Adult , Middle Aged , Prospective Studies , Hydrocortisone/blood , Hydrocortisone/metabolism , Follow-Up Studies , Remission Induction
15.
Front Endocrinol (Lausanne) ; 15: 1410080, 2024.
Article in English | MEDLINE | ID: mdl-39086897

ABSTRACT

Introduction: Patients with Cushing's syndrome (CS) in remission show sustained fatigue, myopathy, and an increased prevalence of sarcopenia. The mechanisms that determine these persistent muscle problems are not well known. We aimed to identify circulating microRNAs (miRNAs) with differential expression that could be potential biomarkers for the diagnosis and/or prognosis in CS. Patients and methods: Thirty-six women in sustained remission for 13 ± 7 years (mean ± SD) from CS, with a median age (IQ range) of 51 (45.2-60) years and mean ± SD BMI of 27 ± 4 Kg/m2, and 36 matched healthy controls were investigated. In 7 patients sarcopenia was present according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Small RNA libraries were generated and indexed using a modified Illumina TruSeq small RNA-sequencing protocol. MiRNAs were identified in plasma using bioinformatic analysis, and validation was carried out using RT-qPCR. For the validation, Taqman probes were performed on QuantStudio 5 equipment (Applied Biosystems). Results: In a first discovery group using RNA-sequencing, plasma samples of 18 CS patients and 18 healthy subjects were investigated; circulating miR-28-5p, miR-495-3p and miR-654-5p were upregulated in CS patients as compared with controls (p<0.05). In a validation study of the 3 upregulated miRNAs in 36 patients and 26 controls, no differences were observed by RT-qPCR; however, the expression of circulating miR-28-5p was upregulated in CS patients with sarcopenia as compared with those without (AUC for fold-change in the ROC analysis, 0.798; p=0.0156). The optimized cut-off value for miR-28-5p to identify CS patients with sarcopenia was 3.80, which yielded a sensitivity of 86% and a specificity of 69%. Conclusion: MiR-28-5p, a muscle-specific microRNA involved in myotube proliferation and differentiation in vivo, may serve as an independent non-invasive biomarker for identifying CS patients at high-risk of sarcopenia despite biochemical remission.


Subject(s)
Biomarkers , Cushing Syndrome , MicroRNAs , Sarcopenia , Humans , Sarcopenia/blood , Sarcopenia/genetics , Female , Middle Aged , Pilot Projects , Cushing Syndrome/blood , Cushing Syndrome/genetics , Cushing Syndrome/diagnosis , MicroRNAs/blood , MicroRNAs/genetics , Biomarkers/blood , Circulating MicroRNA/blood , Circulating MicroRNA/genetics , Case-Control Studies , Prognosis , Remission Induction
16.
Sci Rep ; 14(1): 19451, 2024 08 21.
Article in English | MEDLINE | ID: mdl-39169260

ABSTRACT

Adrenal gland-induced hypertension results from underlying adrenal gland disorders including Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These adrenal disorders are a risk for cardiovascular and renal morbidity and mortality. Clinically, treatment for adrenal gland-induced hypertension involves a pharmaceutical or surgical approach. The former presents very significant side effects whereas the latter can be ineffective in cases where the adrenal disorder reoccurs in the remaining contralateral adrenal gland. Due to the limitations of existing treatment methods, minimally invasive treatment options like microwave ablation (MWA) have received significant attention for treating adrenal gland disorders. A precise comprehension of the dielectric properties of human adrenal glands will help to tailor energy delivery for MWA therapy, thus offering the potential to optimise treatments and minimise damage to surrounding tissues. This study reports the ex vivo dielectric properties of human adrenal glands, including the cortex, medulla, capsule, and tumours, based on the data obtained from four patients (diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma) who underwent unilateral adrenalectomy at the University Hospital Galway, Ireland. An open-ended coaxial probe measurement technique was used to measure the dielectric properties for a frequency range of 0.5-8.5 GHz. The dielectric properties were fitted using a two-pole Debye model, and a weighted least squares method was employed to optimise the model parameters. Moreover, the dielectric properties of adrenal tissues and tumours were compared across frequencies commonly used in MWA, including 915 MHz, 2.45 GHz, and 5.8 GHz. The study found that the dielectric properties of adrenal tumours were influenced by the presence of lipid-rich adenomas, and the dielectric properties of Cushing's syndrome tumour were lowest in comparison to the tumours in patients diagnosed with Conn's syndrome and Pheochromocytoma. Furthermore, a notable difference was observed in the dielectric properties of the medulla and cortex among patients diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These findings have significant implications for the diagnosis and treatment of adrenal tumours, including the optimisation of MWA therapy for precise ablation of adrenal masses.


Subject(s)
Adrenal Gland Neoplasms , Adrenal Glands , Cushing Syndrome , Hypertension , Microwaves , Pheochromocytoma , Humans , Adrenal Gland Neoplasms/surgery , Microwaves/therapeutic use , Adrenal Glands/surgery , Adrenal Glands/pathology , Hypertension/therapy , Pheochromocytoma/surgery , Cushing Syndrome/surgery , Ablation Techniques/methods , Female , Male , Hyperaldosteronism/surgery , Hyperaldosteronism/therapy , Adrenalectomy , Middle Aged
17.
World J Clin Cases ; 12(23): 5431-5440, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39156087

ABSTRACT

BACKGROUND: Primary renal Ewing's sarcoma (ES) is extremely rare, and only two cases causing Cushing's syndrome (CS) have been reported to date. We report that the case of an 18-year-old patient is diagnosed primary renal ES with typical CS characterized by purple stripes, weight gain, and hypertension. CASE SUMMARY: CS was first diagnosed by laboratory testing. A huge tumor was revealed in the kidney following an imaging examination. Moreover, brain and bone metastases were observed. After comprehensive treatment, primarily based on surgery, primary renal ES was pathologically diagnosed with a typical EWSR1-FLI1 genetic mutation through genetic testing. Furthermore, the glucocorticoid level returned to normal. By the ninth postoperative month of follow-up, the patient was recovering well. Cushing-related symptoms had improved, and a satisfactory curative effect was achieved. CONCLUSION: Primary renal ES, a rare adult malignant tumor, can cause CS and a poor prognosis.

18.
Endocr J ; 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39183039

ABSTRACT

Cushing's disease is associated with increased morbidity and mortality. Osilodrostat, a potent oral 11ß-hydroxylase inhibitor, provided rapid, sustained mean urinary free cortisol (mUFC) normalization in Cushing's disease patients in two Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734). Here, we evaluate the efficacy and safety of osilodrostat in Cushing's disease in patients of Asian origin compared with patients of non-Asian origin. Pooled data from LINC 3 and LINC 4 were analyzed. Outcomes were evaluated separately for Asian and non-Asian patients. For the analysis, 210 patients were included; 56 (27%) were of Asian origin. Median (minimum-maximum) osilodrostat dose was 3.8 (1-25) and 7.3 (1-47) mg/day in Asian and non-Asian patients, respectively. mUFC control was achieved at weeks 48 and 72 in 64.3% and 68.1% of Asian and 68.2% and 75.8% of non-Asian patients. Improvements in cardiovascular and metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life were similar in both groups. Most common adverse events (AEs) were adrenal insufficiency (44.6%) in Asian and nausea (45.5%) in non-Asian patients. AEs related to hypocortisolism and pituitary tumor enlargement occurred in more Asian (58.9% and 21.4%) than non-Asian patients (40.3% and 9.1%). Of Asian and non-Asian patients, 23.2% and 13.6%, respectively, discontinued because of AEs. Asian patients with Cushing's disease generally required numerically lower osilodrostat doses than non-Asian patients to achieve beneficial effects. Hypocortisolism-related AEs were reported in more Asian than non-Asian patients. Together, these findings suggest that Asian patients are more sensitive to osilodrostat than non-Asian patients.

19.
Eur J Endocrinol ; 191(3): 334-344, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39171930

ABSTRACT

BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Individuals with PBMAH and glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome due to ectopic expression of the GIP receptor (GIPR) typically harbor inactivating KDM1A sequence variants. Primary unilateral macronodular adrenal hyperplasia (PUMAH) with concomitant glucocorticoid and androgen excess has never been encountered or studied. METHODS: We investigated a woman with a large, heterogeneous adrenal mass and severe adrenocorticotropic hormone-independent glucocorticoid and androgen excess, a biochemical presentation typically suggestive of adrenocortical carcinoma. The patient presented during pregnancy (22nd week of gestation) and reported an 18-month history of oligomenorrhea, hirsutism, and weight gain. We undertook an exploratory study with detailed histopathological and genetic analysis of the resected adrenal mass and leukocyte DNA collected from the patient and her parents. RESULTS: Histopathology revealed benign macronodular adrenal hyperplasia. Imaging showed a persistently normal contralateral adrenal gland. Whole-exome sequencing of 4 representative nodules detected KDM1A germline variants, benign NM_001009999.3:c.136G > A:p.G46S, and likely pathogenic NM_001009999.3:exon6:c.865_866del:p.R289Dfs*7. Copy number variation analysis demonstrated an additional somatic loss of the KDM1A wild-type allele on chromosome 1p36.12 in all nodules. RNA sequencing of a representative nodule showed low/absent KDM1A expression and increased GIPR expression compared with 52 unilateral sporadic adenomas and 4 normal adrenal glands. Luteinizing hormone/chorionic gonadotropin receptor expression was normal. Sanger sequencing confirmed heterozygous KDM1A variants in both parents (father: p.R289Dfs*7 and mother: p.G46S) who showed no clinical features suggestive of glucocorticoid or androgen excess. CONCLUSIONS: We investigated the first PUMAH associated with severe Cushing's syndrome and concomitant androgen excess, suggesting pathogenic mechanisms involving KDM1A.


Subject(s)
Cushing Syndrome , Histone Demethylases , Humans , Female , Adult , Histone Demethylases/genetics , Histone Demethylases/metabolism , Cushing Syndrome/genetics , Cushing Syndrome/pathology , Cushing Syndrome/metabolism , Glucocorticoids , Pregnancy , Androgens/metabolism , Adrenal Glands/pathology , Adrenal Glands/metabolism , Adrenal Glands/diagnostic imaging , Adrenal Hyperplasia, Congenital/genetics , Adrenal Hyperplasia, Congenital/complications , Adrenal Hyperplasia, Congenital/pathology , Adrenal Hyperplasia, Congenital/metabolism
20.
JCEM Case Rep ; 2(8): luae128, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39108602

ABSTRACT

Ectopic ACTH secretion (EAS) accounts for 10% to 20% of all Cushing syndrome cases. Diffuse intrapulmonary neuroendocrine cell hyperplasia (DIPNECH), a poorly understood lung disease, is characterized by abnormal proliferation of neuroendocrine cells in the bronchial mucosa. It is thought to be a precursor of pulmonary carcinoid and has been associated with EAS in a handful of cases. We present 2 patients with clinical, radiological, and pathological features of DIPNECH who presented with florid Cushing syndrome secondary to EAS evidenced by rapid onset of symptoms, elevated plasma ACTH, and cortisol levels, and failed high-dose dexamethasone suppression testing. Treatment of hypercortisolism included excision of the involved lung and medical therapy with steroidogenesis inhibitors. Despite the aggressive initial management, hypercortisolism persisted. This case series highlights the importance of considering DIPNECH as a cause for Cushing syndrome in the appropriate clinical scenario and underscores the likelihood that surgery may not be curative because of the diffuse nature of this disease. Given the high mortality associated with EAS, prompt medical therapy, appropriate prophylaxis, and bilateral adrenalectomy can be lifesaving measures when initial surgery fails.

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